Comparing methods to estimate time-varying reproduction numbers using genomic and epidemiological data

Estimating the time-varying reproduction number [R]t during an epidemic is important. [R]t indicates whether an epidemic is growing or declining and can aid in assessing the impact of interventions. Recent advances have enhanced methods for estimating [R]t and other epidemiological parameters from surveillance and genomic data independently. The Birth-Death Skyline (BDSKY) in BEAST 2.5 and EpiEstim are two common methods used to estimate [R]t from these data sources. We introduce an outbreak simulation platform that generates pathogen sequence data and epidemiological linelists. We use this platform to to assess [R]t estimation methods accuracy under various sampling scenarios similar to what was observed during past epidemics. We identified biases and determined appropriate scenarios for improving the accuracy of [R]t estimation approaches based on multiple outbreak simulations. When data becomes sparse and unreliable, genomic sequence data provide reasonable [R]t estimates even when sampling is not uniform.